More than half of drugs in current late-stage trials for Alzheimer’s disease target beta-amyloid proteins, which stick together to form plaques between nerve cells in the brain of Alzheimer’s patients. These plaques destroy surrounding cells and impair cognition.
Biogen recently announced that its antibody-based therapy, aducanumab, saw a statistically significant reduction in these plaques, as well as a slowing of mental decline at the 12-month mark.
Another group of drugs in the Alzheimer’s pipeline to watch are the beta secretase cleaving enzyme (BACE) inhibitors, which block the production of beta-secretase, an enzyme needed for production of beta-amyloid proteins. By blocking production of the proteins rather than destroying them once they’re formed, it’s hoped these drugs may have a bigger impact.
In August 2016, AZD3293 (Lilly and AstraZeneca), an oral BACE inhibitor, received fast-track designation for the development program in Alzheimer’s disease. A pivotal Phase II/III clinical trial of AZD3293 started in late 2014 and is planned to recruit 1,500 patients and end in May 2019. In April 2016 the company announced it would advance to phase 3 without modification. According to the manufacturer, AZD3293 has been shown in studies to reduce levels of amyloid beta in the cerebro-spinal fluid of people with Alzheimer’s and healthy volunteers.
Another potential target in the treatment of Alzheimer’s are tau proteins, which form tangles inside brain cells. TauRx Pharmaceuticals’ LMTX, a second-generation tau aggregation inhibitor, acts by reducing levels of aggregated or misfolded tau proteins, which are associated with the progressive neurodegeneration which is the hallmark of Alzheimer’s disease, according to the company. At press time, TauRx had completed two large phase 3 clinical trials of LMTX in Alzheimer’s disease.
Flortaucipir (Lilly), a molecular imaging agent under investigation for detecting the presence of amyloid plaque in the brain, has been submitted to the FDA for approval.
According to the Alzheimer’s Association, plaques form when protein pieces called beta-amyloid clump together. Beta-amyloid comes from a larger protein found in the fatty membrane surrounding nerve cells.
“[Alzheimer’s disease] is unique due to the process of diagnosis, which is based on memory impairment, thinking skills, functional abilities and behavioral changes,” says Andrew Lyle, director of business development, Curexa Pharmacy. “Furthermore, the true physical tests that can be completed will only rule out other diagnoses; you can test for amyloid plaques and swelling of the brain but at that point the disease has already taken its toll.”